Immune signaling mechanisms of PTSD risk and symptom development: insights from animal models

Abstract

Post-traumatic stress disorder (PTSD) is characterized by persistent re-experiencing of a traumatic event, avoidance, and increased arousal. The approved pharmacological treatments for PTSD have limited efficacy (~60% treatment response), supporting the need for identification of biomarkers and novel pharmacological therapies. Mounting evidence suggests increased inflammatory markers and altered immune gene expression correlate with the severity of symptoms in PTSD patients. However a causal role of immune signaling in development and maintenance of PTSD symptoms is not clear, as inflammation may also be an epiphenomenon related to metabolic and behavioral effects of stress. Animal studies have been critical in understanding the potential causal role of immune signaling in PTSD. In this review we will present the most recent evidence, primarily focusing on the last 3 years, for inflammatory dysfunction both preceding and following PTSD, and how animal models of PTSD have contributed to our understanding of immune mechanisms involved in enduring anxiety after trauma. We will particularly focus on the role of peripheral vs. central immune signaling, the differences between single vs. chronic stress models of PTSD and recent utilization of these models to investigate novel anti-inflammatory treatments. We also highlight some current gaps in the literature including models of TBI/PTSD comorbidity, lack of translational peripheral markers of inflammation and the relatively incomplete understanding of the inflammatory trajectory after severe stress.